Laxatives are used to treat constipation, i.e. the absence of regular defecation, accumulation of feces in the colon and/or the passage of small amounts of hard, dry stools. People who are constipated may find it difficult and painful to have a bowel movement. Laxatives are also used to cleanse the lower bowel before a proctoscopy, rectoscopy, colonoscopy, x-ray imaging of the colon or similar diagnostic procedure. There are several types of laxatives, see overview in Table 1. Laxatives can produce side effects, but usually not serious ones. Stimulants and irritants are more likely than other types of laxatives to cause side effects such as abdominal discomfort, faintness and cramps. Laxatives may be for oral administration, e.g. tablets, capsules and liquids, or for rectal administration, e.g. suppositories and enemas. Orally administered laxatives can reduce bioavailability of drugs and nutrients.
Castor oil is a well known laxative, a usual therapeutic adult dose for laxative effect is 15 to 60 mL, administered orally. About 90% of the fatty acid content in castor oil is the triglyceride formed from ricinoleic acid (12-hydroxy-9-cis-octadecenoic acid), a monounsaturated fatty acid, which is the active component of castor oil, acts as a laxative by stimulating secretion of fluid and electrolytes in the small intestines. One or two copious of semi-fluid stools are released within 2 to 6 hours of the administration. Ricinoleic acid is effective in preventing the growth of numerous species of viruses, bacteria, yeasts and molds, and it does possess some anti-inflammatory effect (Vieira et al. 2000; Burdock et al. 2006). Short chain fatty acids, such as lactic, acetic, butyric and propionic acid, can stimulate colonic motility and by increasing the osmotic pressure (i.e. hyperosmotic agents, Table 1).
Lubiprostone (difluoropentyl-2-hydroxy-6-oxooctahydrocyclopenta-heptanoic acid) is a bicyclic fatty acid derived from a metabolite of prostaglandin E1. After oral administration lubiprostone activates specific chloride channels (C1C-2 channels) in the gastro-intestinal tract to stimulate intestinal fluid secretion, increase GI transit, and improve symptoms of constipation (B. E. Lacy 2008). Thus, lubiprostone has a receptor specific effect.
TABLE 1Types of laxativesClassSite of actionOnset of actionMechanism of actionExamplesBulk-producingSmall and12-72hoursIncrease the volume of thePsyllium,agentslarge intestinestool (retain more water),methylcellulose,and will both soften thedietary fibersstool and stimulateintestinal motility.StoolSmall and12-72hoursHold water and fats withinDocusate (asofteners andlarge intestinethe stool, making it easiersurfactant)surfactantsto move along.SalineSmall and0.5-6hoursRetain water in theMagnesiumlarge intestineintestinal lumen, increasinghydroxide,intraluminal pressuremagnesium sulfate,leading to softer stool.sodium phosphateLubricants andColon6-8hoursMake the stool slippery soMineral oilemollientsthat it slides through theintestine more easily.Retards absorption ofwater.HyperosmoticColon0.5-3hoursAct by the osmotic effectSorbitol, lactulose,agentsthat retains water within thepolyethyleneintestineglycol, glycerinsuppositoriesStimulantsColon6-10hoursStimulate peristaltic action,Bisacodyl tablets,and irritantsi.e. contraction of smoothsennaColon6-8hoursmuscles that propelPhenolphthaleinSmall intestine2-6hourscontents through theCastor oilColon0.25-1hourdigestive tract.BisacodylsuppositoriesFoodsFigs, olive oil,prunes
It has been documented that saturated and unsaturated fatty acids possess both antibacterial and antiviral activity, and that the fatty acids play a role in the natural defense against infections in mucosal membranes and skin, see e.g. Kabara (1978). In vitro studies have shown that free fatty acids kill enveloped viruses, such as Herpes simples-1 and Herpes simplex-2, Gram-positive bacteria, Gram-negative bacteria, such as Helicobacter pylori, and fungi (see Khulushi et al. (1995), Thormar et al. (2007), Carballeira (2008)).
The dietary and nutritional benefits of essential fatty acids are well known and dietary supplements such as fish oils have been used for a long time, providing poly-unsaturated fatty acids (PUFAs), also referred to as highly-unsaturated fatty acids (HUFAs), in the form of triacylglycerides (TAGs) also called triglycerides. The so called essential omega-3 fatty acids are particularly beneficial.
EP 420056 discusses that fat base suppositories, in particular those based on non-lauric cocoa butter substitute, can cause irritation which is induce by the fat base. The document suggests to add to the suppositories fatty acids, fatty acid salts or fatty acid esters to reduce the irritation caused by the fat base.
New laxatives with little side effects and discomfort would be much appreciated.